The role of leucocytes in the acetyl salicylic acid (aspirin) induced nitric oxide synthesis in the production of interferon-α, a potent inhibitor of platelet aggregation and a thrombolytic agent

The role of aspirin-induced NO synthesis in the production of interferon-α (IFN-α) in leucocytes and the effect of IFN-α on platelet aggregation was studied. Treatment of Platelet Rich Plasma (PRP) with the dialyzed supernatant from the leucocyte suspension incubated with 80 μM aspirin resulted in parallel syntheses of NO and IFN-α as determined by methemoglobin assay and enzyme linked immunosorbent assay respectively. Incubation of PRP with 10 nM purified IFN-α for 40 min resulted in the maximal inhibition of platelet aggregation through the synthesis of NO due to the activation of nitric oxide synthase in platelets by IFN-α. The treatment of clotted PRP with IFN-α resulted in the lysis of the clot due to the fibrinolysis. Injection of IFN-α was found to protect mice from death due to the lysis of ADP-induced coronary thrombus. Interferon-α was found to be a potent inhibitor of platelet aggregation and a thromboprotective agent. Part of this work was published as an abstract in the proceeding of the Annual Workshop in Biological Sciences, Calcutta, 2005. An erratum to this article can be found at     

老年急性缺血性脑卒中患者早期阿斯匹林治疗的临床对照研究

目的：探讨老年急性缺血性脑卒中早期抗血小板治疗效果,以及降低致残率的临床观察,方法：采用随机双盲对照研究,对入院48小时内急性脑卒中患者,经头颅CT扫描除外脑出血,无阿斯匹林禁忌的给予160mg 1/日口服或安慰剂治疗四周,结果：共入选180例,住院期间阿斯匹林组死亡2例,对照组死亡3例,阿斯匹林组治疗期间63％基本恢复,无再发脑卒中及出血,两组治疗结果比较判别显著（P＜0．05）, 结论：阿斯匹林辅佐治疗,不影响其它常规治疗,药源方便,价廉,具有促进恢复,预防复发作用。     

阿司匹林对急性脑梗死患者血浆一氧化氮及血小板α颗粒膜蛋白的影响

目的　探讨阿司匹林对急性脑梗死患者血浆一氧化氮 (NO)及血小板α颗粒膜蛋白 (GMP 14 0 )的影响。方法　 2 0 0 2 - 0 5～ 2 0 0 3- 0 8广东江门市人民医院 78例急性脑梗死患者随机分为 4 0例治疗组和 38例对照组 ,采用硝酸酶还原法和双抗体夹心酶联免疫吸附法分别测定治疗组和对照组的血浆NO及GMP 14 0的含量。治疗组患者经过阿司匹林治疗后 2周 ,再次测定治疗组和对照组的血浆NO及GMP 14 0的含量。结果　治疗组治疗后患者血浆NO及GMP 14 0水平较对照组治疗后明显下降 (P <0 0 1) ,治疗组治疗后的ESS分值高于对照组治疗后的ESS分值 (P <0 0 1)。结论　阿司匹林能通过降低急性脑梗死患者血浆NO及GMP 14 0的水平 ,从而减轻缺血性脑损伤 ,起到脑保护作用。     

Hepatoprotective effect of nitric oxide in experimental model of acute hepatic failure

AIM: To evaluate the effect of nitric oxide (NO) on the development and degree of liver failure in an animal model of acute hepatic failure (AHF).METHODS: An experimental rat model of galactosamine-induced AHF was used. An inhibitor of NO synthase, nitroarginine methyl ester, or an NO donor, arginine, were administered at various doses prior to or after the induction of AHF.RESULTS: All tested groups developed AHF. Following inhibition of the endogenous NO pathway, most liver parameters improved, regardless of the inhibitor dose before the induction of liver damage, and depending on the inhibitor dose after liver damage. Prophylactic administration of the inhibitor was more effective in improving liver function parameters than administration of the inhibitor after liver damage. An attempt to activate the endogenous NO pathway prior to the induction of liver damage did not change the observed liver function parameters. Stimulation of the endogenous NO pathway after liver damage, regardless of the NO donor dose used, improved most liver function parameters.CONCLUSION: The endogenous NO pathway plays an important role in the development of experimental galactosamine-induced AHF.     

Efficacy of a New Accelerated Streptokinase Regime in Acute Myocardial Infarction: A Double Blind Randomized Clinical Trial

Background: Studies of thrombolysis in acute ST‐elevation myocardial infarction (STEMI) have focused on differences in outcome between groups receiving various regimes. Expedited treatment may influence the efficacy of nonfibrin specific thrombolytic agents in restoring early patency of the infarct‐related artery (IRA), which is a major determinant of survival after ST‐elevation myocardial infarction (STEMI). Methods: We performed a randomized double blind clinical trial comparing an accelerated infusion (1.5 MU/20 min; group A, n = 200) with the conventional infusion (1.5 MU/60 min; group B, n = 100) of streptokinase (SK) in 300 patients with their first episode of acute STEMI. Demographics, clinical reperfusion rates, angiographic study findings, left ventricular ejection fraction (LVEF), in‐hospital morbidity and mortality and one year mortality were compared between two groups. Results: Mean age was 59 ± 12 years (79% male). There were no differences in baseline data between groups. Clinical, electrocardiographic and physiologic reperfusion indices revealed significant faster and higher reperfusion rates and better preserved LVEF at discharge in group A. Sixty‐three percent of patients in either group underwent invasive coronary angiography at a mean of 5 days with comparable findings. Atrial fibrillation, malignant ventricular arrhythmias in the second day, in‐hospital and late mortalities rates occurred more frequently in group B patients. In multivariate analysis, accelerated SK infusion was the only independent predictor of higher electrocardiographic reperfusion (OR = 3.2, CI: 1.93–5.3, P < 0.001). Conclusions: The accelerated SK infusion regimen of 1.5 MU in 20 min is safe and well tolerated with significantly faster and higher clinical reperfusion rates, more preserved LV systolic function, less atrial and ventricular sustained arrhythmias, and less in‐hospital and 1 year mortality rates in acute STEMI.     

阿司匹林联合氯吡格雷治疗短暂性脑缺血发作临床疗效观察

目的探讨阿司匹林联合氯吡格雷在治疗短暂性脑缺血发作（TIA）中的疗效。方法选取2008年10月至2009年10月北京市第六医院神经内科收治的36例前循环TIA患者为研究对象,所有患者均应用无创性经颅多普勒超声（TCD）诊断技术观察到微栓子信号（MES）。将其随机分为观察组（18例）和对照组（18例）,其中观察组患者采用阿司匹林联合氯吡格雷的方法进行治疗,而对照组则单纯采用阿司匹林进行治疗,其他治疗两组相同。以30d为1个疗程,疗程结束后对效果进行比较分析。结果观察组患者TIA发作频率明显低于对照组（P〈0．05）,应用TCD诊断技术观察MES显著减少（P〈0．05）。结论阿司匹林联合氯吡格雷治疗TIA效果肯定,优于单用阿司匹林。     

老年冠心病患者血浆一氧化氮水平及其意义

目的探讨老年冠心病患者血浆一氧化氮（ＮＯ）水平及意义。方法以５０例老年冠心病患者和３０例经检查确认无心血管疾病和糖尿病的老年人为研究对象。结果冠心病组血浆ＮＯ含量均值为３０．５３８±７．４４４ｍｏｌ／Ｌ,对照组为３７．２００±８．８６３ｍｏｌ／Ｌ,差异显著（Ｐ＜０．０５）。结论老年冠心病组血浆ＮＯ水平明显低于对照组。     

不同剂量阿司匹林对急性冠状动脉综合征炎性标志物和预后的影响

目的 观察不同剂量阿司匹林对急性冠状动脉综合征(ACS)患者炎性标志物和临床预后的影响.方法 将ACS患者随机分为不同剂苗阿司匹林治疗组(A组100 mg/d、B组500 mg/d和C组1000 mg/d)治疗和随访1年,检测各时段炎性标志物水平,并记录有关临床事件.结果 共入选312例,A组106例,B组104例,C组102例.所有入选者基线超敏C反应蛋白(hsCRP)、IL-6、TNFα均显著高于正常参考值,应用不同剂量阿司匹林治疗1、6、12个月后,炎性标志物均下降,治疗前后各指标比较差异均有统计学意义,但各组间比较差异无统计学意义.3组急性冠状动脉事件发生率差异无统计学意义,B、C组发生胃肠道不适症状者较A组增加.结论 ACS患者血清炎性标志物升高,应用阿司匹林治疗后炎性标志物水平显著下降,但大剂量阿司匹林(500～1000 mg)未见炎性标志物水平进一步下降和再发心脏事件减少,而胃肠道不良反应有所增加.     

急性心肌梗死患者溶栓前后患者血浆中NO、vWF的动态观察

目的　探讨急性心肌梗死 (AMI)溶栓前后患者血浆中NO、vWF的动态变化及其临床意义。方法　对 4 1例AMI溶栓前及溶栓后 2h、2 4h分别采血 ,测取血浆中NO及vWF的含量 ,并进行统计学处理比较。结果　 2 4例溶栓再通后2h ,患者血浆中NO显著降低 ,P <0 0 1,vWF无明显变化 >0 0 5 ;2 4h ,患者血浆中NO显著增高 ,P >0 0 1,vWF显著降低 ,P <0 0 1;而未再通组溶栓后 2h、2 4hNO及vWF的含量均无显著差异P >0 0 5。结论　AMI溶栓再通患者血浆中NO明显增高 ,vWF明显下降 ;溶栓后无再通患者血浆中NO和vWF无明显变化     

不同剂量阿司匹林对冠心病患者血清C－反应蛋白水平的影响

目的探讨不同剂量阿司匹林对冠心病患者血清C－反应蛋白水平的影响。 方法选取2017年1月至2018年3月青岛市城阳区人民医院收治的120例冠心病患者作为观察组,将所有患者按随机数表法分为甲组、乙组、丙组,各40例,选取40例同期健康体检者作为对照组。甲、乙、丙组患者均接受阿司匹林口服治疗,甲组用药剂量为50 mg/d,乙组用药剂量为150 mg/d,丙组用药剂量为300 mg/d,用药时长为1个月。对比治疗前后各组对象血清C－反应蛋白水平。 结果观察组冠心病患者血清C－反应蛋白水平均为(4.75±0.18)mg/L,对照组健康体检者血清C－反应蛋白水平为(2.82±1.09)mg/L。观察组血清C－反应蛋白水平高于对照组,差异有统计学意义(P<0.05)。治疗前,甲、乙、丙3组患者血清C－反应蛋白水平差异无统计学意义(P>0.05)。甲、乙两组患者治疗后血清C－反应蛋白水平与治疗前比较,差异无统计学意义(P>0.05),丙组患者治疗后C－反应蛋白水平低于治疗前(P<0.05),且低于甲、乙两组治疗后水平(P<0.05)。 结论冠心病患者血清C－反应蛋白水平高于健康人群,大剂量(300 mg/d)阿司匹林能够能够有效降低C－反应蛋白水平。     

冠心病患者C反应蛋白的临床意义及阿司匹林的影响

目的 :探讨 C反应蛋白 (CRP)与冠心病 (CHD)的关系及阿司匹林对其的影响。方法 :观察 6 9例冠状动脉单支狭窄 >6 0 %的 CHD患者 ,35例正常对照者及 31例病例对照者的 CRP浓度及不同剂量的阿司匹林对CRP浓度的影响 ,及 CRP浓度的高低与冠状动脉狭窄程度的关系。结果 :CHD患者的 CRP浓度较正常对照组显著增高 (P <0 .0 5 ) ,大剂量的阿司匹林可降低 CHD患者的 CRP浓度 (P <0 .0 5 ) ,CRP浓度与冠状动脉狭窄程度正相关 (r =0 .5 3,P <0 .0 5 )。结论 :CRP浓度可作为评价冠状动脉病变严重程度的一个参考指标     

Low-dose aspirin increases aspirin resistance in patients with coronary artery disease

PURPOSE: We sought to investigate the association of aspirin dose and aspirin resistance in stable coronary artery disease patients measured by a point-of-care assay. METHODS: We studied 468 consecutive stable coronary artery disease patients in a referral cardiac center who were taking aspirin 80 to 325 mg daily for > or =4 weeks. The VerifyNow Aspirin (Ultegra RPFA-ASA, Accumetrics Inc, San Diego, Calif) was used to determine aspirin responsiveness. An aspirin reaction unit (ARU) > or =550 indicates the absence of aspirin-induced platelet dysfunction, based on correlation with epinephrine-induced light transmission aggregometry. Demographic and clinical data were collected to analyze the predictors of aspirin resistance. RESULTS: Aspirin resistance was noted in 128 (27.4%) patients. Univariate predictors of aspirin resistance include elderly (P = 0.002), women (P <0.001), anemia (P <0.001), renal insufficiency (P = 0.009) and aspirin dose < or =100 mg (P = 0.004). Multivariate analysis revealed hemoglobin (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.51 to 0.69; P <0.001) and aspirin dose < or =100 mg (OR 2.23; 95% CI 1.12 to 4.44; P = 0.022) to be independent predictors of aspirin resistance. Daily aspirin dose < or = 100 mg was associated with increased prevalence of aspirin resistance compared with 150 mg and 300 mg daily (30.2% vs 16.7% vs 0%, P = 0.0062). CONCLUSION: A 100 mg or less daily dose of aspirin, which may have lower side effects, is associated with a higher incidence of aspirin resistance in patients with coronary artery disease. Prospective randomized studies are warranted to elucidate the optimal aspirin dosage for preventing ischemic complications of atherothrombotic disease.     

阿托伐他汀对冠心病患者血清一氧化氮及一氧化氮合酶含量的影响

目的　观察阿托伐他汀对冠心病患者血清一氧化氮 (NO)及一氧化氮合酶 (NOS)含量水平的影响。方法　对用阿托伐他汀治疗的 79例冠心病患者依据是否合并高胆固醇血症分为两组 ,对其治疗前后血清 NO及 NOS含量水平进行对比分析。结果　不论是否合并高胆固醇血症的冠心病 ,阿托伐他汀均可升高其血清 NO及 NOS水平。结论　阿托伐他汀可通过调脂治疗抑制脂质的过氧化反应 ,保护血管内皮功能 ,但其保护内皮功能的作用不受患者是否存在高脂血症的影响 ,改善内皮功能 ,对冠心病的防治具有重要意义。     

多学科协作模式改变缺血性卒中超早期重组组织型纤溶酶原激活剂静脉溶栓的预后

目的探讨多学科协作(MDT)模式下急性缺血性卒中(AIS)超早期重组组织型纤溶酶原激活剂(rtPA)静脉溶栓标准化诊疗流程实施的效果。方法将164例rt-PA静脉溶栓治疗的超早期AIS患者纳入研究,其中MDT模式下rt-PA静脉溶栓标准化诊疗流程实施前34例被设为实施前组,实施后130例被设为实施后组。对比分析两组患者到达医院至溶栓治疗时间(DNT)、美国国立卫生研究院卒中量表(NIHSS)评分和改良Rankin量表(mRS)评分及溶栓流程中各个环节(患者到达急诊至电话启动溶栓流程、神经内科住院总医师接诊患者、开始CT扫描和签署知情同意书)的用时情况。结果 DNT均值由标准化流程实施前的111.76±24.84 min缩短到标准化流程实施后的81.31±15.13 min,差异具有统计学意义(P0.001)。溶栓治疗前两组患者NIHSS评分对比差异无统计学意义(P0.05),治疗后两组患者NIHSS评分均较治疗前显著改善(P0.01),实施后组患者出院时NIHSS评分及mRS评分较实施前组明显降低(P0.01)。实施前后两组患者急诊至开始CT扫描时间比较差异无统计学意义(P0.05);但实施后组患者到达急诊至电话启动溶栓流程时间、患者到达急诊至神经内科住院总医师接诊患者时间和患者到达急诊至签署知情同意书时间均显著低于实施前组(P0.01)。结论 MDT模式下rt-PA静脉溶栓标准化诊疗流程的实施有助于缩短DNT,提高静脉溶栓治疗效果和改善预后。     

华法林与阿司匹林和氯吡格雷三重抗栓治疗的安全性

目的观察有华法林抗栓指征的患者,冠状动脉(简称冠脉)支架植入术后,联合华法林、阿司匹林和氯吡格雷三重抗栓治疗的安全性。方法选择23例心房颤动(有1项以上危险因素)、机械瓣置换术后和左室血栓的患者,冠脉植入药物洗脱支架后,联合华法林、阿司匹林和氯吡格雷(三重抗栓组)治疗,严格控制国际标准化比值(INR)1.6～2.5,观察1年总的和严重出血事件的发生率。分别选择同期86例冠心病患者,植入冠脉支架后应用阿司匹林和氯吡格雷(双重抗血小板组)治疗,64例有华法林抗凝指征的患者,应用华法林抗凝(抗凝组)治疗(INR2.0～3.0)进行比较。结果三重抗栓组1年总的出血发生率为17.4%,与双重抗血小板组(4.7%)比较有显著性差异(P<0.05),而与抗凝组(10.9%)比较差异无显著性。严重出血事件三重抗栓组显著高于其他两者(13.3%vs 1.2%,4.7%,P<0.01或0.05)。结论三重抗栓治疗明显增加患者出血的发生率。     

急性脑梗死超早期的r-tPA溶栓治疗

目的　探讨重组组织型纤溶酶原激活物 (r- t PA)溶栓治疗发病 6h内脑梗死的疗效及并发症。方法　共收集本院 2 0 0 1～ 2 0 0 3年 43例溶栓治疗的急性脑梗死病例 ,其中 32例经静脉溶栓 ,1 1例经动脉溶栓。分别对两组病例进行溶栓前后的 NIHSS,ESS及 ADL量表评分 ,根据 3个月时的随访记录判断溶栓疗效 (分为治愈、显效、有效、无效 )。结果　静脉溶栓组和动脉溶栓组的总有效率分别为 79.3%、90 .9% ;治愈率分别为2 7.6%、45.5% ,溶栓后脑出血率分别为 1 0 .3%、1 8.2 % ,但由于动脉组例数较少 ,两组疗效差异无统计学意义。结论　 6 h内溶栓治疗是安全有效的 ,低 NIHSS的患者有较好转归。     

Determinants of aspirin resistance in patients with type 2 diabetes

BackgroundCardiovascular disease is a leading cause of mortality among patients with type 2 diabetes mellitus (T2DM). Numerous patients with T2DM show resistance to aspirin treatment, which may explain the higher rate of major adverse cardiovascular events observed compared with non-diabetes patients, and it has recently been shown that aspirin resistance is mainly related to accelerated platelet turnover with persistent high platelet reactivity (HPR) 24 h after last aspirin intake. The mechanism behind HPR is unknown. The aim of this study was to investigate the precise rate and mechanisms associated with HPR in a population of T2DM patients treated with aspirin.MethodsIncluded were 116 consecutive stable T2DM patients who had attended our hospital for their yearly check-up. HPR was assessed 24 h after aspirin intake using light transmission aggregometry (LTA) with arachidonic acid (AA) and serum thromboxane B2 (TXB2) measurement. Its relationship with diabetes status, insulin resistance, inflammatory markers and coronary artery disease (CAD) severity, using calcium scores, were investigated.ResultsUsing LTA, HPR was found in 27 (23%) patients. There was no significant difference in mean age, gender ratio or cardiovascular risk factors in patients with or without HPR. HPR was significantly related to duration of diabetes and higher fasting glucose levels (but not consistently with HbA_1c), and strongly related to all markers of insulin resistance, especially waist circumference, HOMA-IR, QUICKI and leptin. There was no association between HPR and thrombopoietin or inflammatory markers (IL-6, IL-10, indoleamine 2,3-dioxygenase activity, TNF-α, C-reactive protein), whereas HPR was associated with more severe CAD. Similar results were found with TXB2.ConclusionOur results reveal that ‘aspirin resistance’ is frequently found in T2DM, and is strongly related to insulin resistance and severity of CAD, but weakly related to HbA_1c and not at all to inflammatory parameters. This may help to identify those T2DM patients who might benefit from alternative antiplatelet treatments such as twice-daily aspirin and thienopyridines.     

Statins in the first-line therapy of acute coronary syndrome – similar to aspirin?

Statins are cholesterol-lowering drugs, highly effective in the primary and secondary prevention of coronary artery disease. It has been found, however, that statins also have nonlipid effects; they can influence different pathways, which have been described to participate in the pathogenesis of acute coronary syndrome (ACS). Inflammation or decreased production of nitric oxide are obvious targets for statin therapy. Recently, several large clinical trials have been published, showing safety and, in some areas, efficacy of administration of statins early after ACS. Furthermore, there is growing evidence from both experimental and small clinical studies that statin therapy may have favourable effects when started as soon as possible after the development of ACS. Confirmation of this approach by large randomized trials is needed; however, based on currently available data, statins have high chance of achieving a similar place in the first-line therapy of ACS as the pillar of contemporary therapeutic strategy, aspirin.     

老年2型糖尿病合并冠心病患者阿司匹林抵抗的危险因素分析

目的 研究老年T2DM合并冠心病患者对阿司匹林的反应性及其危险因素. 方法 选择我院老年科住院的T2DM合并冠心病患者147例,根据血栓弹力图（TEG）结果将其分为阿司匹林抵抗组（AR,抑制率≤50％）和阿司匹林非抵抗组（N-AR）,并分析两组临床数据. 结果 AR组30例,N-AR组117例.AR发生率为20％.AR组同型半胱氨酸（Hcy）、FPG、TG、LDL-C及HbA1c分别为（16.43±4.77）mmol/L,（7.73±0.16）mmol/L,（1.70±0.60） mmol/L,（2.60±0.55） mmol/L,（7.79±0.58）％,均明显高于N-AR组,而视黄醇结合蛋白（RBP）为（34.17±9.30） mmol/L,低于NAR组（P＜0.05）.Logistic回归分析结果显示,FPG、TC、LDL-C和Hcy是AR的影响因素,使患者AR的危险性分别提高1.9倍,0.1倍,13.1倍和1.1倍.血糖不达标者、糖尿病病程较长者AR发生率增高（P＜0.05）.结论 T2DM合并冠心病患者存在一定的AR现象,有效地控制血糖,减低血脂,降低Hcy,可降低AR发生率.     

阿司匹林片联合氯吡格雷片对短暂性脑缺血发作的疗效观察

目的探讨对短暂性脑缺血发作以阿司匹林片联合氯吡格雷片进行治疗所具有的临床效果。方法选择曾在我院接受治疗的短暂性脑缺血发作患者106例,将这些患者平均分为两组,并且将这两组分别作为观察组与对照组,对照组中患者单纯以阿司匹林进行治疗,观察组中患者在对照组治疗基础上联合氯吡格雷片进行治疗,观察两组患者的临床治疗有效率以及血小板变化情况,并对其进行观察吡较。结果在经过治疗之后,观察两组患者的临床治疗有效率,观察组中患者的治疗总有效率为94.3%,对照组中患者的治疗总有效率为75.5%,两组患者存在显著差异;观察两组患者的血小板功能变化情况,两组患者均在一定程度上得到改善,但观察组中患者的改善情况明显优于对照组,两组患者之间差异明显。结论对短暂性脑缺血发作以阿司匹林片联合氯吡格雷片进行治疗,可取得较理想临床效果,有着很高的临床治疗有效率,能够使患者的血小板能够得到有效改善,缓解患者的临床症状,使患者尽快恢复健康,可在临床上进行广泛应用。